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Brokken-Wiersinga-Prummel loop

German: Brokken-Wiersinga-Prummel-Regelkreis

1 Definition

The Brokken-Wiersinga-Prummel loop (also known as Prummel-Wiersinga feedback control) is a ultrashort feedback mechanism that links the concentration of thyrotropin in the anterior pituitary gland to its own secretion.

2 Physiology

It is assumed that TSH binds to thyrotropin receptors on folliculostellate cells in the anterior pituitary. The inhibition of TSH secretion from thyrotropic cells may be mediated by thyrostimulin.

The Brokken-Wiersinga-Prummel loop is part of the multi-loop thyrotropic feedback control. Its biological benefit may result from prevention of excessively high TSH levels and from generation of TSH pulsatility

3 Clinical Impact

The Prummel-Wiersinga loop may be a challenge for diagnostical interpretation of laboratory results, especially in patients with Graves' disease, where TRAbs suppress TSH secretion independently from and additionally to the current levels of free thyroxine. This results in TSH levels that are lower than expected in relation to FT4 levels. Therefore in Graves' disease, thyrotropin levels cannot be the sole criterion for therapeutic decisions, e.g. regarding dosing of thyrostatic agents.

4 Background

The eponymous authors demonstrated the existence of the feedback loops in the human pituitary and its clinical significance. However, the processing structure has first been described in 1986 in rabbits by Kakita and Odell.

5 References

  1. Kakita, T. und Odell, W. D. (1986). Pituitary gland: one site of ultrashort-feedback regulation for control of thyrotropin. AJP - Endocrinology and Metabolism; 250(2) E121-E124. PMID 3082213
  2. Prummel MF, Brokken LJ, Meduri G, Misrahi M, Bakker O, Wiersinga WM.: Expression of the thyroid-stimulating hormone receptor in the folliculo-stellate cells of the human anterior pituitary. J Clin Endocrinol Metab. 2000 Nov;85(11):4347-53. PMID 11095478
  3. Brokken LJ, Scheenhart JW, Wiersinga WM, Prummel MF.: Suppression of serum TSH by Graves' Ig: evidence for a functional pituitary TSH receptor. J Clin Endocrinol Metab. 2001 Oct;86(10):4814-7. PMID 11600546
  4. Brokken LJ, Wiersinga WM, Prummel MF.: Thyrotropin receptor autoantibodies are associated with continued thyrotropin suppression in treated euthyroid Graves' disease patients. J Clin Endocrinol Metab. 2003 Sep;88(9):4135-8. PMID 12970276
  5. Dietrich, J. W., A. Tesche, C. R. Pickardt, U. Mitzdorf: Thyrotropic Feedback Control: Evidence for an Additional Ultrashort Feedback Loop from Fractal Analysis. Cybernetics and Systems 2004; 35(4): 315-31.
  6. Prummel MF, Brokken LJ, Wiersinga WM: Ultra short-loop feedback control of thyrotropin secretion. Thyroid. 2004 Oct; 14(10): 825-9. PMID 15588378
  7. Brokken LJ, Bakker O, Wiersinga WM, Prummel MF: Functional thyrotropin receptor expression in the pituitary folliculo-stellate cell line TtT/GF. Exp Clin Endocrinol Diabetes. 2005 Jan; 113(1): 13-20. PMID 15662590

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